Modulation of Genes Responsible for Cilia Length by Exposure to Cigarette Smoke

Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Patients with COPD have difficulty clearing mucus and debris from their airways. Even smokers who have not developed COPD may have difficulty clearing the airways. This is partly because smoking impairs the function of cilia, tiny hairs lining the airways that sweep out mucus to keep the airways clean. The investigators have found that smoking reduces the length of cilia, which may contribute to the worsened cilia function in smoking and COPD. This is true even in smokers who show no signs of lung disease. The investigators believe that smoking affects levels of genes in lung cells, resulting in shorter cilia.

Study Overview

• Status: Completed
• Conditions: Smoking; COPD

Detailed Description

In this study, we will use bronchoscopy (inserting a scope into the lungs) to obtain lung cells by brushing cells from the airways and we will study genes that may be related to cilia length. Our goals are (1) to prove that exposure to cigarette smoke results in shorter cilia, (2) to learn which specific genes control cilia length, and (3) to learn how smoking affects the gene ODF2 and what effect this has on cilia. Understanding how smoking affects cilia may help us identify new ways to treat patients with COPD.

• Study Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study will involve healthy nonsmokers and healthy smokers.

Description

Inclusion Criteria:

• Must be capable of providing informed consent
• Males and females, age 18 or older
• Nonsmoking, validated by venous carboxyhemoglobin and urine nicotine and cotinine within range for nonsmoker without smoke exposure, matched with smoker group by age, sex, ethnic/racial group
• Good overall health without history of chronic lung disease, including asthma, and without recurrent or recent (within 3 months) acute pulmonary disease
• Normal physical examination
• Normal routine laboratory evaluation, including general hematologic studies, general serologic/immunologic studies, general biochemical analyses, and urine analysis
• Negative HIV, hepatitis B and C serology
• Normal chest X-ray (PA and lateral)
• Normal electrocardiogram
• Females - not pregnant
• No history of allergies to medications to be used in the bronchoscopy procedure
• Not taking any medications relevant to lung disease or having an effect on the airway epithelium
• Willingness to participate in the study

Exclusion Criteria:

• Unable to meet the inclusion criteria
• Pregnancy
• Current active infection or acute illness of any kind
• Habitual use of drugs and/or alcohol within the past six months (Acceptable: -Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria)
• Evidence of malignancy within the past 5 years

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Group 1; Healthy non-smokers
Group 2; Healthy non-smokers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence that exposure to cigarette smoke will result in shorter cilia length in human airway epithelial	Cilia length will be measured using three preparation techniques: air-dried cytospins, detached cilia on cytospins, and mounted hydrated aliquots of cells.	One Year

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 20, 2014

Study Record Updates

• Last Update Posted (Estimate): May 2, 2016
• Last Update Submitted That Met QC Criteria: April 29, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: COPD; Smoker; Cilia; Nonsmoker; Cigarette Smoke; ODF2
• Other Study ID Numbers: 1102011549

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED